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Biomedical subjects

H U Aeschbacher

Publications and source records attributed to H U Aeschbacher.

At least 19 recordsLinked to original sources
PubMed1992

Natural antioxidants as inhibitors of oxygen species induced mutagenicity.

A ternary antioxidant vitamin mix consisting of ascorbic acid, alpha-tocopherol and lecithin as well as a rosemary extract with carnosic acid and carnosol as the two major active ingredients were shown to exhibit strong antimutagenic effects in Ames tester strain TA102. This strain has been shown to be highly sensitive to reactive oxygen species. Mutagenicity was induced by the generation of oxygen radicals by tert-butyl-hydroperoxide (tBOOH) or hydrogen peroxide (H2O2); therefore, the antimutagenic property of the above substances was attributed to their antioxidant properties. In the case of the vitamin mix, ascorbic acid was held responsible for this inhibitory property, whereas for the rosemary extract carnosic acid was identified as the antimutagenic agent. Since oxygen radicals are known to be involved in the multiprocess of carcinogenicity, it is concluded that these antioxidants might exhibit anticarcinogenic properties.

Antimutagenic Agents↗
PubMed1991

Formation of heterocyclic amines during meat extract processing and cooking.

Standardized biological in vitro systems and in particular those used for cancer prediction are being used to monitor the development of food products in order to ensure the absence of potential mutagens or carcinogens. Maillard reactions occurring during meat extract production was followed in order to reduce the formation of heterocyclic amines. Possibilities to reduce the content of heterocyclic amines during meat extract processing have been proposed. However, several aspects, such as interaction with food-borne mutagen or carcinogen inhibitors, keeping quality, and organoleptic properties have also been taken into consideration. Whenever possible, food contaminants must be analytically determined and compared to total intake exposure and tolerated levels of other comparable food contaminants to establish realistic "tolerated" contamination levels.

Amines↗
PubMed1990

Inhibition by coffee of nitrosourea-mediated DNA damage in mice.

Oral administration of coffee at doses ranging from 150 mg to 1 g per kg body weight significantly decreased endogenously formed nitrosourea-mediated DNA damage in bone marrow as well as in colon epithelial cells in mice that had simultaneously received oral administration of methylurea and sodium nitrite. Since coffee (1 g/kg body weight) did not decrease DNA damage when administered orally together with performed methylnitrosourea, it was hypothesized that coffee inhibits nitrosation in the stomach of mice. The lowest effective level of coffee, when compared on the basis of body weight, corresponds to a human intake of about 5 cups of coffee. Both chlorogenic acid (150 mg/kg body weight) and premelanoidins (1 g/kg body weight), which occur as ingredients in, or are formed during roasting of, coffee, were shown to inhibit nitrosourea-induced DNA damage in mice.

Administration, Oral↗
PubMed1989

Contribution of coffee aroma constituents to the mutagenicity of coffee.

About 40 coffee aroma constituents belonging to the classes of dicarbonyls, sulphur-containing compounds, furfuryls, N-heterocyclics and others were systematically evaluated in three Ames tester strains. Only aliphatic dicarbonyl compounds showed notable direct mutagenic activity, which mainly affected 'base-pair substitution' in Ames tester strains TA100 and TA102. Very weak effects were also seen with some N-heterocyclics, mainly affecting frameshift tester strain TA98 upon metabolic activation. However, it was shown that these N-heterocyclics do not contribute substantially to the mutagenicity in coffee. The hydrogen peroxide and methylglyoxal contents of coffee were determined up to 26 hr after preparation. Their concentrations tended to decrease whereas mutagenic activity decreased significantly with time in tester strains TA100 and TA102. It is concluded that several highly labile coffee constituents contribute to the bacterial mutagenicity and also that the synergism between hydrogen peroxide and methylglyoxal is not the main factor. The absence of coffee mutagenicity/carcinogenicity in rodents with these highly reactive coffee aroma compounds can be explained in part by detoxification of microsomal enzyme systems.

Chromatography, Gas↗
PubMed1989

Purification of the food-borne carcinogens 2-amino-3-methylimidazo [4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in heated meat products by immunoaffinity chromatography.

A rapid and simple scheme has been developed for the isolation and purification of two of the major mutagenic heterocyclic amines formed in heated beef products by affinity chromatography using monoclonal antibodies which recognize 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Two cell lines producing IgG antibodies were established following fusion of Sp2 or P3x.63 myeloma cells with spleen cells of immunized BALB/cby mice. The antigen was bovine gamma globulin haptenized with 2-(3-carboxypropylthio)-3-methylimidazo-[4,5-f]quinoline. The antibodies were immobilized on CNBr-activated Sepharose 4B. IQ and MeIQx formed in heated beef products were partially purified by XAD-2 chromatography and then applied to the affinity columns. Purification by affinity chromatography was adequate for subsequent quantitative analysis by HPLC with UV detection. With this purification scheme as little as 1 g of beef extract or 15 g of fried beef could be assayed for IQ and MeIQx at the part per billion level. Both antibodies had similar affinity constants for IQ (9.3 X 10(6) and 6.7 X 10(6) M-1) and for MeIQx (7.1 X 10(5) and 2.7 X 10(5) M-1) and both were suitable for immunoaffinity purification of IQ from complex mixtures. MAb2 could be used as well to selectively remove MeIQx from meat products after partial purification by XAD-2. MAb1, despite having a 3-fold higher affinity than MAb2 for MeIQx, could not be used for affinity chromatography for this mutagen.

Animals↗
PubMed1989

Effect of heterocyclic amines and beef extract on chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes.

Two of the major bacterial mutagens formed in heated meat products, 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline or the basic fraction of beef extract induced a low frequency of sister chromatid exchanges in human lymphocyte cultures in the presence of metabolic activation. Structural chromosome aberrations were not induced at comparable high concentrations in human lymphocytes with intact repair system, suggesting that repair or induction of point mutations are involved in the DNA-damaging effect of heterocyclic amines rather than structural chromosome aberrations. Accordingly it may be concluded that mammalian cells with both intact repair and enzyme systems are more relevant than bacterial systems for evaluating the carcinogenic potential of heterocyclic amines.

Animals↗
PubMed1989

An efficient and convenient method for the purification of mutagenic heterocyclic amines in heated meat products.

A simple and efficient method for the purification of mutagenic heterocyclic amines from heated meat products has been developed. In only two steps, namely extraction of raw material on Kieselgur followed by medium pressure liquid chromatography on Sephasorb HP, very clean fractions with high recovery rates of mutagenic compounds were obtained, thus allowing isolation and quantitation by high performance liquid chromatography (HPLC) with UV detection. The method was validated on both food grade and bacterial beef extracts as well as fried beef. In 1-5 g samples of beef extracts, levels up to 70 p.p.b. (ng/g) of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), 8-90 p.p.b. of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and up to 8 p.p.b. of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) were determined. In fried beef, 1 p.p.b. of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 1 p.p.b. of MeIQx were measured. The quantitative results of beef samples were in agreement with results from determinations using immunoaffinity chromatography/HPLC or liquid chromatography coupled with mass spectrometry. MeIQx could be quantified in fried beef down to 1 ng/g of fresh beef material. According to assays performed with reference standards of tryptophan and glutamic acid pyrolysis products, the method could also be extended to quantitate other heterocyclic amines.

Amines↗
PubMed1988

Analysis of mutagenic heterocyclic amines in cooked beef products by high-performance liquid chromatography in combination with mass spectrometry.

Mutagenic activity detected in beef extracts and in fried beef heated for varying periods of time was purified and then analysed by high-performance liquid chromatography in combination with mass spectrometry (LC-MS). The major mutagenic component found in all of the beef products was identified as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) followed by lesser amounts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx). Identification and quantification of mutagens were achieved by the use of deuterium-labelled analogues. Measured levels of MeIQx and 4,8-DiMeIQx in different batches of beef extract were in the range 11.7-52.2 and 0-11.2 ng/g, respectively, and in beef heated at 275 degrees C for 5-15 min the values of MeIQx and 4,8-DiMeIQx were in the range 2.7-12.3 and 0-3.9 ng/g, respectively. The levels of IQ found in beef extracts were 0-36.8 ng/g and in fried beef the amounts were estimated at 0.3-1.9 ng/g. The method of purification is rapid, requiring only XAD-2 adsorption followed by an acid-base liquid partition against ethyl acetate and blue cotton treatment (trisulpho-copper-phthalocyanine) prior to LC-MS analysis. Because of the sensitivity of LC-MS, mutagens present in cooked beef can be detected at the low parts-per-billion-level and as little as 10 g of cooked beef was required for analysis.

Animals↗
PubMed1988

Metabolism of the food-borne mutagen/carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the rat: assessment of biliary metabolites for genotoxicity.

The absorption and kinetics of excretion of [14C]2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) was studied in male Sprague-Dawley rats. Within 72 hr of an oral dose of [14C]MeIQx (20 mg/kg) 33-56% of the radioactivity was excreted in the urine and 37-75% of the radioactivity in the faeces, which accounted for greater than 99% of the dose. Only low levels of radioactivity remained in the body. Radioactivity, when expressed per gram of tissue, was highest in the liver and kidney with smaller amounts detected in the lung and both the small and large intestines. Between 25 and 50% of a dose of MeIQx was recovered in the bile within 24 hr. Biliary metabolites were excreted over a long period of time with one radioactive fraction rapidly excreted at 2-3 hr and a second fraction excreted at 10-12 hr. The metabolites present in bile were assessed for genotoxicity using Salmonella typhimurium TA98 with or without hepatic S-9 activation and were found to be present as detoxified products. The residual mutagenic activity present in bile was attributed primarily to unmetabolized MeIQx.

Animals↗
PubMed1988

Major routes of metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the rat.

The metabolic fate of 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), a carcinogen formed in cooked meat and fish, has been investigated in male Sprague-Dawley rats. Five metabolites were recovered from bile of animals given an intragastric dose of [2-14C]MeIQx. These accounted for nearly all of the radioactivity in bile. The chemical structures of these metabolites were elucidated by proton NMR, UV and mass spectroscopy. Three structures may be assigned unambiguously: two sulfamates, N-(3,8-dimethylimidazo [4,5-f]quinoxalin-2-yl)sulfamic acid and N-(8-hydroxy-methyl-3-methylimidazo[4,5-f]quinoxalin-2-yl) sulfamic acid, and one glucuronide, N2-(beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f ]quinoxaline. In addition, an acetyl and a glucosiduronyl conjugate of 5-hydroxy-MeIQx were observed. The spectral evidence did not allow an unambiguous assignment of the site of conjugation. The two glucuronides were excreted in urine and the sulfamate of MeIQx was found in feces as well as urine. All five metabolites were found to be non-mutagenic to Salmonella typhimurium TA98 with or without metabolic activation. The glucuronide conjugates were found also to be non-mutagenic when beta-glucuronidase was incorporated with S-9 mixture in the mutation assay, and thus all appear to be detoxification products. The previously reported metabolite, 2-amino-8-hydroxymethyl-3-methylimidazo[4,5-f]quinoxaline which is mutagenic to Salmonella typhimurium TA98 with metabolic activation, was identified as a minor component in both urine and feces.

Animals↗
PubMed1987

Comparison of the mutagenic activity of various brands of food grade beef extracts.

The mutagenic activity of 9 brands of commercial meat extracts were compared using Ames tester strain TA 98 with hepatic S-9 activation prior to concentration by solvent extraction. In a preincubation test system where 20 mg of intact meat extract preparations were tested per plate, about half of the brands were non-mutagenic whereas the other half increased the spontaneous revertant number by a factor of 2.5-3 (MF). The mutagenic principals could be extracted into methylene chloride under alkaline conditions and the mutagenic activity of these basic organic extracts ranged in potency from a mutation factor of 7-40 (280-1600 revertants) per 2 g equivalents of intact meat extracts in the standard Ames test. A quantitative correlation was obtained between the two trials (intact and extracted samples). The commercial meat extract with the greatest activity contained approximately 70 ng/g of total amino-imidazoquinoline and amino-imidazoquinoxaline compounds while the weakest brand of meat extract contained less than 10 ng/g of these heterocyclic aromatic amines. The human intake of these heterocyclic amines from meat extract in bouillon soups was estimated at maximally 100 ng/day and is approximately 10(3) times less than the estimated total daily intake of all heterocyclic amines which are known to be formed in protein-rich heated foods.

Animals↗
PubMed1986

Rates of micronuclei induction in different mouse strains.

It has previously been shown that the inbred mouse strain MS/Ae was more sensitive in the micronucleus test to several mutagenic agents than outbred mice. To elucidate the possible influence of inbreeding, several inbred strains including MS/Ae, AKR, BALB/c, C57 BR were compared to the two OF1 and NMRI outbred strains. The 3 mutagenic agents MNNG, MMC and MMS all induced a significantly higher number of micronuclei in the MS/Ae strain than in any of the other mouse strains. AKR was especially resistant to the alkylating agents MMS and MNNG. Hence, except for the MS/Ae mouse strain, no inbred strain showed a systematically higher sensitivity than the outbred strains for all of the 3 mutagenic agents used.

Animals↗
PubMed1986

The effect of caffeine in the in vivo SCE and micronucleus mutagenicity tests.

Caffeine which was administered per os to outbred mice either twice, 30 and 6 h before sacrifice or once, 30 h before sacrifice, at dose levels of 50, 75 or 100 mg/kg body weight only caused a weak induction of micronuclei at the highest dose. Again a level of 100 mg caffeine per kg body weight was required before a weak but not significant effect could be observed in the micronucleus test using a mutagen-sensitive inbred strain of mice. In Chinese hamsters caffeine doses of 45, 75, 150 or 300 mg/kg body weight either given once or twice per os at the same time schedule as used for the mice also caused a clear cut induction of micronuclei only at the highest dose level. In the SCE test with Chinese hamster again 300 mg of caffeine were necessary to obtain a mutagenic effect although this test is considered to be more sensitive to mutagenic damage than the micronucleus test. It can therefore be concluded that caffeine causes DNA damage only at dose levels in the LD50 range which is higher for hamsters than for mice.

Animals↗
PubMed1985

Instant and brewed coffees in the in vitro human lymphocyte mutagenicity test.

Incubation of instant and 'home brew' coffees (caffeinated and decaffeinated) and of coffee aroma with cultured human lymphocytes in the presence and absence of S-9 increased the number of total aberrations. However, the increase was smaller in the presence of S-9 than in its absence. Pure caffeine tested with or without S-9 at doses equivalent to levels in caffeine-containing coffee did not give statistically significant increases of any type of aberration when compared with controls. In all in vitro test systems used to date, coffee and coffee aroma or their reactive compounds were metabolically deactivated in the presence of S-9. This could explain the negative results obtained in mutagenicity assays in vivo.

Animals↗
PubMed1984

Investigation of coffee in sister chromatid exchange and micronucleus tests in vivo.

Administration of a single oral dose of instant coffee to Chinese hamsters at levels up to 2.5 g/kg body weight did not increase the frequency of sister chromatid exchanges. Furthermore, five consecutive daily oral doses of instant coffee given to Swiss OF-1 mice up to 3 g/kg/day did not induce increases in micronuclei above spontaneous levels. Similarly, no effect was observed in the micronucleus test after mice received two oral doses of coffee aroma of up to 50 ml/kg.

Animals↗